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Abstract

The work presented here was performed in conjunction with an experimental group in order to prove the concept that an alternating magnetic field (AMF) could be used to induce an intramolecular cyclization to effect payload release. The system studied here consisted of a fluorophore tethered to gold-coated iron oxide nanoparticles (Fe3O4 NPs) via an organic linker consisting of 2 key elements: a carbonate (electrophile) and an amine (nucleophile). Connected to the carbonate was the fluorophore, anthracene, which was attached to the organic linker system by means of an oxime ether linkage. This thesis work served as the control group for the study by examining the absence of the amine. The control linker system was synthesized over 5 steps with a 53% overall yield. The amine-deficient control system, containing a thiol and carbonate group, was then covalently bound to gold-coated Fe3O4 NPs. The system was then subjected to an alternating magnetic field to promote local hyperthermia which would drive payload release for the experimental group but not for the control group due to the lack of a nucleophilic element. The control system was subjected to the AMF and analytical methods were performed on the supernatant of the solution by matrix-assisted laser desorption/ionization time of flight (MALDI-TOF). Results concluded that the control system withstood AMF exposure and retained its payload. Further studies were performed using lithium aluminum hydride (LAH) and dithiothreitol (DTT) on the control system in order to prove that the payload was indeed present on the system. Comparing the results obtained on the control system with that of the experimental system, intramolecular cyclization is proven to be the preferred mechanism of payload release.

Lay Summary

In this work, the control group of a gold nanoparticle-bound molecular delivery system was designed and tested. The purpose of this work was to prove that a payload is released by a specific mechanism. The control system was designed by removing one vital atom responsible for an important role in the mechanism. With this one atom missing, the payload would be unable to release, thus proving that release likely occurs by this proposed cyclization mechanism. After testing the control system, it was discovered that no payload had released, thus supporting the proposed mechanism. Additional testing was performed in order to prove that the payload was indeed attached to the control system. With this evidence in hand, we conclude that the molecular release system occurs by the cyclization mechanism that was hypothesized.